Advertisement

The flavonoid quercetin induces changes in mitochondrial permeability by inhibiting adenine nucleotide translocase

  • Rosalba Ortega
  • Noemí García
Article

Abstract

This study shows the effects of the flavonoid quercetin on diverse mitochondrial functions, among them membrane permeability. Our findings indicate that the addition of 50 µM quercetin did not produce reactive oxygen derived species; however, it inhibited the oxidative stress induced after the addition of Fe2/H2O2 by about 38%. At this concentration, quercetin also promoted a fast calcium release, inhibited oxidative phosphorylation, stimulated oxygen consumption, and decreased membrane potential. In addition 50 µM quercetin inhibited the adenine nucleotide translocase (ANT) by 46%. These effects induced the opening of the permeability transition pore and release of cytochrome c, by its interaction with a component of the non-specific pore complex, fixed to the carrier in the conformation c, as carboxyatractyloside does. Quercetin-induced permeability transition pore opening was inhibited by 0.5 µM cyclosporin A, but, interestingly, the release of cytochrome c was not inhibited by the immunosuppressor, as quercetin was found to disrupt the outer membrane.

Keywords

Flavonoids Quercetin Permeability transition Mitochondria Adenine nucleotide translocase Cytochrome c Calcium 

References

  1. Akerman KEO, Wikström MFK (1976) FEBS Lett. 68:191–197CrossRefGoogle Scholar
  2. Belyaeva EA, Glazunov VV, Korotkov SM (2004) Acta Biochim. Pol. 51:545–551Google Scholar
  3. Bernardi P (1999) Physiol. Ver. 79:1127–1155Google Scholar
  4. Borutaite V, Budriunaite A, Morkuniene R, Brown GC (2001) Biochim. Biophys. Acta 1537:101–109Google Scholar
  5. Borutaite V, Jekabsone A, Morkuniene R, Brown GC (2003) J. Mol. Cell. Cardiol. 35:357–366CrossRefGoogle Scholar
  6. Brookes PS, Digerness SB, Parks DA, Darley-Usmar V (2002) Free Rad. Biol. Med. 32:1220–1228CrossRefGoogle Scholar
  7. Brustovetsky N, Klingenberg M (1996) Biochemistry 35:8483–8388CrossRefGoogle Scholar
  8. Cano A, Arnao MB, Williamson G, Garcia-Conesa MT (2002) Redox Rep. 7:379–383CrossRefGoogle Scholar
  9. Chávez E, Holguín JA (1988) J. Biol. Chem. 263:3582–3597Google Scholar
  10. Chávez E, Moreno-Sánchez R, Zazueta C, Reyes-Vivas H, Arteaga D (1991) Biochim. Biophys. Acta 1070:461–466CrossRefGoogle Scholar
  11. Chow JM, Shen SC, Huan SK, lin HY, Chen YC (2005) Biochem Pharmacol 69:1839–1851CrossRefGoogle Scholar
  12. Correa F, Soto V, Zazueta C (2007) Int. J. Biochem. Cell. Biol. 39:787–798CrossRefGoogle Scholar
  13. Davies AM, Hershman S, Staley GJ, Hoek JB, Peterson J, Cahill A (2003) Nucleic Acids Res. 31:1364–1373CrossRefGoogle Scholar
  14. Dorta DJ, Pigoso AA, Mingatto FE, Rodrigues T, Prado IM, Helena AF, Uyemura AS, Santos AC, Curti C (2005) Chem. Biol. Interact. 152:67–78CrossRefGoogle Scholar
  15. Finucane DM, Bossy-Wetzel E, Waterhouse NJ, Cotter TG, Green DR (1999) J Biol Chem 274:2225–2233CrossRefGoogle Scholar
  16. Franco JL, Braga HC, Stringari J, Missau FC, Posser T, Mendes BG, Leal RB, Santos AR, Dafre AL, Pizzolatti MG, Farina M (2007) Chem Res Toxicol. 20:1919–1926CrossRefGoogle Scholar
  17. García N, García JJ, Correa F, Chávez E (2005) Life Sci. 29:2873–2880CrossRefGoogle Scholar
  18. García N, Martínez-Abundis E, Pavón N, Chávez E (2007) Cell. Biochem. Biophys. 49:84–90CrossRefGoogle Scholar
  19. García N, Zazueta C, Carrillo R, Correa F, Chávez E (2000) Mol. Cell. Biochem. 209:119–123CrossRefGoogle Scholar
  20. García-Sáez AJ, Chintia S, Salgado J, Schwille P (2007) Biophys J 93:103–112CrossRefGoogle Scholar
  21. Gunter TE, Pfeiffer DR (1990) Am J Physiol 258:C755–C786Google Scholar
  22. Halestrap AP (2004) Nature 430:1CrossRefGoogle Scholar
  23. Haworth RA, Hunter DRM (2000) J Bioenerg Biomembr 32:91–96CrossRefGoogle Scholar
  24. Hu JP, Calomme M, Lasure A, De Bruyne T, Pieters L, Vlietinck A, Vanden Berghe DA (1995) Biol. Trace Elem. Res. 47:327–331CrossRefGoogle Scholar
  25. Kokoszka JE, Waymire KG, Levy SE, Sligh JE, Cai J, Jones DP, MacGregor GR, Wallace DC (2004) Nature 29:461–465CrossRefGoogle Scholar
  26. Kowaltowski AJ, Netto LES, Vercesi AE (1988) J. Biol. Chem. 273:12766–12769CrossRefGoogle Scholar
  27. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) J. Biol. Chem. 193:450–457Google Scholar
  28. Metodiewa D, Jaswal AK, Cenas N, Dickancaité E, Segura-Aguilar J (1999) Free Rad. Biol. 26:107–116CrossRefGoogle Scholar
  29. Ohkawa H, Ohishi N, Yagi K (1979) Anal Biochem. 95:351–358CrossRefGoogle Scholar
  30. Park C, So HS, Shin CH, Baek SH, Monn BS, Shin SH, Lee HS, Lee DW, Park R (2003) Biochem Pharmacol 66:1287–1295CrossRefGoogle Scholar
  31. Pebay-Peyroula E, Gonzalez-Dahout C, Kahn R, Trézéguet V, Lauquín GJM, Brandolín G (2003) Nature 426:39–44CrossRefGoogle Scholar
  32. Petrosillo G, Ruggiero FM, Pistolese M, Paradies G (2004) J. Biol. Chem. 279:53103–53108CrossRefGoogle Scholar
  33. Robeszkiewicz A, Balcerczyk A, Bartosz G (2007) Cell Biol Int. 31:1245–1250CrossRefGoogle Scholar
  34. Saija A, Scalese M, Lanza M, Marzullo D, Bonina F, Castelli F (1995) Free Radic Biol Med 19:481–486CrossRefGoogle Scholar
  35. Santos AC, Uyemura SA, Lopes JL, Bazon JN, Mingatto FE, Curti C (1998) Free Rad. Biol. Med. 24:1455–1461CrossRefGoogle Scholar
  36. Scarpa A, Brinley FJ, Tiffert T, Dubyak GR (1978) Ann. N. Y. Acad. Sci. 307:86–112CrossRefGoogle Scholar
  37. Schlesinger PH, Saito M (2006) Cell Death Differ 13:1403–1408CrossRefGoogle Scholar
  38. Schweizer M, Durrer P, Richter C (2004) Biochem. Pharmacol. 48:967–973CrossRefGoogle Scholar
  39. Sekher Pannala A, Chan TS, O’Brien PJ, Rice-Evans CA (2001) Biochem. Biophys. Res. Commun. 282:1161–1168CrossRefGoogle Scholar
  40. Trumbeckaite S, Bernatoniene J, Majiene D, Jakstas V, Savickas A, Toleikis A (2006) Biomed. Pharmacother. 60:245–248CrossRefGoogle Scholar
  41. Wätjen W, Michels G, Steffan B, Niering P, Chovolou Y, Kampkötter Tran-Thi Q, Proksch P, Kahl R (2005) J. Nutr. 135:525–531Google Scholar
  42. Weiss JN, Korge P, Honda HM, Ping P (2003) Circ Res 93:292–301CrossRefGoogle Scholar
  43. Wieckowski MR, Wojtczak L (1998) FEBS Lett. 423:339–342CrossRefGoogle Scholar
  44. Winkel-Shirley B (2002) Curr. Opin. Plant. Biol. 5:218–223CrossRefGoogle Scholar
  45. Zazueta C, Sánchez C, García N, Correa F (2000) Int. J. Biochem. Cell Biol 32:1093–1101CrossRefGoogle Scholar
  46. Zoratti M, Szabó I, De Marchi U (2005) Biochim. Biophys. Acta 1706:40–52CrossRefGoogle Scholar
  47. Zorov DB, Juhaszova M, Sollott SJ (2006) Biochim. Biophys. Acta 1757:509–517CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  1. 1.Departamento de BioquímicaInstituto Nacional de CardiologíaMexicoMexico

Personalised recommendations